Replies to post #273012 on NorthWest Biotherapeutics Inc (NWBO)

[GoodGuyBill]

Do we know if the SAP has been submitted and if the FDA made comments?

You can take that to the bank. The FDA/Hahn and Pazdur are on board. They understand the new immunological paradigm. The FDA guidelines have been written with a lot of carefully thought input from NWBO. There has been discussion about P-values and their application. However, they don't necessarily apply when everyone is living longer including late vaccination. Linda's letter is on point wrt to P-values and sub-groups This is an important area and has been addressed extensively in the SAP on which the FDA has made comments. BTW, would not doubt that several of the 800 statisticians were involved with NWBO. JMHO.

[highwayman4life]

Pazdur speaking specifically in cancer immunotherapy space:

Clinical trials are more than a way to test new therapies. They offer very sick people hope and a chance for more time with their loved ones. Lately, the drug development process has turned into an exercise in me-tooism — at patients’ expense. It’s time to shift the focus back to those who matter most.

During a recent panel discussion, Richard Pazdur, who directs the Food and Drug Administration’s Oncology Center of Excellence, called for companies to reevaluate their current clinical trial processes. He rightfully criticized the industry’s repeated attempts at testing an approach in a disease indication after it has failed multiple times.

With six checkpoint inhibitors on the market, do patients and their doctors really need more of the same? While these drugs are transformative for some, they don’t help the majority of people who take them. What’s more, their use is usually accompanied by harsh side effects. Despite this, the Cancer Research Institute estimates that a whopping 2,250 clinical trials are currently underway for PD-1 or PD-L1 agents — 748 more trials than a little over a year ago.

Is this really the best we can do or strive for? When people enroll in cancer clinical trials, they are placing their lives in our hands. Many have advanced disease and turn to a clinical trial for hope and possible healing. Yet as an industry, we are competing for these patients to test me-too drugs with significant toxicity, sometimes based on marginal preclinical data.

Pazdur said that patients are not a company’s resource. He’s right. They are people who are hoping for a chance at recovery, or at least more time with their families with reasonable quality of life. We should treat patients who volunteer for clinical trials the way we would treat our mothers or husbands or best friends.

Pazdur asked companies to be more efficient by collaborating, sharing data, and conducting platform trials. Some biopharmaceutical companies are trying to do this, but the industry has a long way to go. We should be moving drugs into clinical development only when there’s a strong understanding of disease biology and substantial evidence that a drug has the potential to truly improve lives.

This means rethinking what is an acceptable toxicity profile for a cancer drug and no longer accepting that feeling horribly ill is par for the course for cancer treatments. The drug industry has spent more money to develop more oncology drugs in the last few years than ever before, yet we have not made significant headway in providing broadly effective cancer therapies with limited toxicity. It’s a given that effective oncology treatment will involve combinations of drugs. We need to identify those combinations that offer the appropriate risk for the benefit and allow for a reasonable quality of life.

To develop effective cancer drugs that are well-tolerated, we must slow down and invest the time and dollars at the earliest stages of cancer biology, as well as in preclinical and early-stage clinical trials, ideally leveraging key biomarkers to accurately measure a drug’s effects and identify responders, in order to evaluate if a drug is really worth pushing through late-stage studies into larger populations. Along the way, each company bringing drugs to clinical trials should always be asking: Would I give this drug to a loved one?

By raising the bar, we can give people with cancer new drugs that give them more time with their families and friends without debilitating side effects. We owe it to the millions of people diagnosed with cancer who are looking towards clinical trials as their last hope. And we should accept nothing less.

Pazdur warned that he and the FDA are not pleased with the current state of affairs in the biopharmaceutical industry. We need to take this rebuke to heart, seriously reevaluate our current processes, and once again put patients at the heart of clinical trials.

https://www.statnews.com/2019/09/04/me-too-drugs-cancer-clinical-trials/
LOL...@statnews

Rather than FDA’s oncology CEO, Pazdur likes to think of himself as the oncology CIO: the Chief Innovation Officer. In that role, he can both be at the forefront of new developments in oncology R&D – like tissue-agnostic approvals and the development of neoadjuvant therapies – while also thinking up new ways to make the drug development and review process more efficient.

Pazdur’s dual role as director of the Oncology Center of Excellence and acting director of the Center for Drug Evaluation & Research’s Office of Oncologic Diseases (known inside FDA as “double-O-D”) means he can create innovative regulatory programs and drive their implementation in the review divisions. “If I want something done … I say ‘let’s do it, and they are more than willing,’” he said during a podcast interview. (For the audio of the interview, see link at the bottom of the story.)

“Project Orbis” is a perfect example of Pazdur’s “think it/do it” mentality. Aware that patients in other countries often do not have access to oncology breakthroughs as soon as those in the U.S., Pazdur created a parallel review pilot program with regulatory authorities in Canada and Australia, using the approval Eisai Inc.’s Lenvima (lenvatinib) in combination with Merck & Co. Inc.’s Keytruda (pembrolizumab) in advanced endometrial carcinoma. (Also see "US FDA’s Project Orbis Could Streamline Global Clinical Trials In Cancer" - Pink Sheet, 17 Sep, 2019.)

https://www.focr.org/news/pink-sheet-richard-pazdur-20th-anniversary-edition

Pazdur is most certainly onboard as is Hahn and change is coming! I too believe our tiny biotech company/NWBO has been at a minimum, very thought provoking as to the changes we are seeing and will be seeing in the FDA/OCE/CDER.

The safety profile is most certainly there for DCVax and IMO the clinical benefit will be there as well. Is it possible we get Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients? Think Priority Review..I think the chances are very good!

Here's to interesting times to come!